I. Field
The present disclosure relates generally to novel capsazepine derivatives, their use in pharmaceutical compositions, methods of using the compounds for treating diseases.
II. Description of Related Art
Advanced oral cancer has a 70% death rate that has not changed in over 30 years. Furthermore, the pain associated with inoperable oral cancer is reported to be the worst symptom by these patients and there are no drugs available that effectively alleviate this pain. Patients with inoperable tumors in the head and neck experience intense pain as the tumor continues to grow and invade critical structures. Opioids are the main drugs used to manage pain and to provide palliative care, however these patients quickly develop tolerance to these drugs resulting in little to no pain management and a very slow and painful death. As these tumors grow they frequently invade neurovascular structures resulting in intense pain and they often rupture the carotid artery resulting in death. Reduction in tumor volume and blockage of TRPV1 channels not only prevents invasion of critical structures but also provides a better quality of life and may prove useful in palliative care for patients undergoing treatment and patients at end-of-life. Oral cancer patients' tumors are accessible and frequently are inoperable because they invade or are approximated upon critical structures in the head and neck. Many oral cancer patients die from tumor invasion of the carotid artery. This leaves no treatment options for this patient population. Administering capsazepine, especially direct injection of capsazepine into these tumors, results in reduction of tumor volume and can prevent tumor invasion of nerve bundles and critical structures such as the carotid artery (WO 2014/089067). The development of additional compounds to treat these cancers and other cancers represents an important clinical challenge.